Aortic aneurysms are weakened/bulging areas in the aorta, the largest blood vessel in the body. Abdominal aortic aneurysms (“AAAs”) are significantly more common in men, and are the 10th leading cause of death in men over age 55. In fact, annual deaths from ruptured AAAs may be as high as 30,000, which is comparable to the number of annual deaths from prostate cancer or breast cancer.
Abdominal aortic aneurysms are generally identified through screening of patients with specific health histories that suggest that they may be candidates for aneurysms. Studies have found that mortality can be reduced for patients with large aneurysms through surgical intervention. However, for small aneurysms, such intervention has not proven to improve survival rates, so such patients are monitored but remain untreated.
Arterial calcification, such as that which occurs in atherosclerosis (i.e. hardening of the arteries), has been reported to be associated with a high risk of adverse clinical events. Recent studies have suggested that the calcification of arteries is an organized and regulated process with many similarities to bone mineralization. The mineralization of bone is controlled by a balance of the actions of osteoblast cells (which deposit minerals such as calcium) and osteoclast cells (which resorb minerals and decalcify bone). Similarly, the calcification of arterial plaques in subjects with atherosclerosis is hypothesized to be controlled by osteoblast-like cells and osteoclast-like cells. However, the mechanism is not understood, and studies have, paradoxically, shown that patients that have osteoporosis, in which excessive osteoclast activity causes bone demineralization (out of balance with osteoblast activity), also have high arterial calcification (too much mineralization of the arteries). Similarly, studies have suggested that treating subjects with bisphosphonates, a class of osteoporosis drug that inhibits osteoclasts, has the dual benefit of improving bone density and reducing arterial calcification.
Since aneurysms result from the weakening, rather than the hardening, of arteries, it is not yet clear whether calcification is physiologically relevant to the formation and progression of aneurysms. Though it was once assumed that aneurysms occurred as a consequence of advanced atherosclerosis, increasing evidence suggests that they may be distinct (if somewhat related) phenomena that share a few, but not all, clinical risk factors.
At present, aneurysms are treated by either endovascular techniques (endovascular stent graft) or open surgery techniques. Open techniques include bypass surgery with a prosthetic graft and excision. Bypass surgery of an aneurysm means placing the prosthetic graft to cut off blood flow through the aneurysm. If the aneurysm is infected or mycotic, it may then be excised (cut out and removed from the body). If uninfected, the aneurysm is often left in place.
For aneurysms in the aorta, arms, legs, or head, the weakened section of the vessel may be replaced by a bypass graft that is sutured at the vascular stumps. Instead of sewing, the graft tube ends, made rigid and expandable by nitinol wireframe, can be inserted into the vascular stumps and permanently fixed there by external ligature. New devices were recently developed to substitute the external ligature by expandable ring allowing use in acute ascending aorta dissection, providing airtight, easy and quick anastomosis extended to the arch concavity. Less invasive endovascular techniques allow covered metallic stent grafts to be inserted through the arteries of the leg and deployed across the aneurysm.
As can be appreciated from the above discussion, a need exists for improved clinical therapies to prevent and/or treat aneurysms. Accordingly, it is one of the purposes of the present invention to treat vascular and especially abdominal aortic aneurysms, by providing a method of preventing their formation, but without being subject to undesirable side effects or requiring intrusive or invasive interventions. It is another purpose of the invention to provide a method of inducing the regression of established aneurysms to cause the vessel to return to a safer and relatively more normal state.